Peripheral expression of MAPK pathways in Alzheimer's and Parkinson's diseases

Abstract

Alteration of mitogen-activated protein kinase pathways may cause aberrant protein phosphorylation and enhanced apoptosis in Alzheimer's disease (AD) and Parkinson's disease (PD). Increased susceptibility of lymphocytes to apoptosis has been reported in AD. To our knowledge this is the first study to investigate the expression and phosphorylation status of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) in peripheral blood lymphocytes of 20 AD and 20 PD patients and 20 healthy controls using western blot analysis. Compared with controls, no significant difference of total p38MAPK or JNK levels were observed in AD and PD patients, whereas phosphorylated p38MAPK and phosphorylated JNK levels were significantly increased in the AD and PD groups (p<0.001). However, the increased levels of the two phosphorylated kinases in AD versus PD patients presented no significant difference. Interestingly, phosphorylated p38MAPK and phosphorylated JNK levels were positively correlated with disease duration (r=0.602, p=0.005 and r=0.561, p=0.010, respectively) and negatively correlated with the Mini Mental State Examination score (r=-0.664, p=0.001 and r=-0.578, p=0.008, respectively) in AD patients. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of p38MAPK and JNK may lead to the development of innovative biomarkers of neurodegenerative diseases, particularly for AD.

Keywords: Alzheimer’s disease; Mitogen-activated protein kinase; Parkinson’s disease; Peripheral blood lymphocytes; c-Jun N-terminal kinase.